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A 48-year-old woman presented with isolated sixth cranial nerve palsy. She subsequently developed systemic lupus erythematosus (SLE) based on clinical and laboratory parameters. Three years later, she presented again with sixth cranial nerve palsy affecting the contralateral eye. Within 2 weeks of steroid initiation, complete recovery occurred. The unusual rare presentation of SLE in the current patient, as well as the pathogenesis and treatment of cranial neuropathy in SLE are discussed. [ABSTRACT FROM AUTHOR]

Apical membrane antigen-1 (AMA1) is a conserved malarial vaccine candidate essential for the formation of tight junctions with the rhoptry neck protein (RON) complex, enabling Plasmodium parasites to invade human erythrocytes, hepatocytes, and mosquito salivary glands. Despite its critical role, extensive surface polymorphisms in AMA1 have led to strain-specific protection, limiting the success of AMA1-based interventions beyond initial clinical trials. Here, we identify an i-body, a humanised single-domain antibody-like molecule that recognises a conserved pan-species conformational epitope in AMA1 with low nanomolar affinity and inhibits the binding of the RON2 ligand to AMA1. Structural characterisation indicates that the WD34 i-body epitope spans the centre of the conserved hydrophobic cleft in AMA1, where interacting residues are highly conserved among all Plasmodium species. Furthermore, we show that WD34 inhibits merozoite invasion of erythrocytes by multiple Plasmodium species and hepatocyte invasion by P. falciparum sporozoites. Despite a short half-life in mouse serum, we demonstrate that WD34 transiently suppressed P. berghei infections in female BALB/c mice. Our work describes the first pan-species AMA1 biologic with inhibitory activity against multiple life-cycle stages of Plasmodium. With improved pharmacokinetic characteristics, WD34 could be a potential immunotherapy against multiple species of Plasmodium., (© 2024. The Author(s).)

Objectives: The primary objective was to develop an educational video to teach patients with rheumatoid arthritis (RA) self-assessment of their disease activity. Secondary objectives were to validate the video, identify the challenges in producing it, and the responses to these challenges., Methods: Rheumatologists from 7 Middle Eastern Arab countries (MEAC) discussed unmet needs in the education of patients with RA. They reviewed pre-existing educational audiovisual material and drafted the script for a new video in Arabic. The video was produced in collaboration with a technical team, then validated by patients using a standardized interview. At each step of production, challenges were identified., Results: Twenty-three rheumatologists from MEAC identified unmet needs in patients' education. A video was produced, explaining the concepts of treat-to-target and showing a patient performing self-assessment using DAS-28. Sixty-two patients were interviewed for validation and found the video to be useful and easy to understand, albeit not replacing the physician's visit. Most common challenges encountered included acceptance of patient empowerment, agreement on DAS-28 as composite measure, production of a comprehensible written Arabic text, and addressing the population cultural mix., Conclusion: Despite challenges, the video was well accepted among patients and can be used for clinical and research purposes. It is particularly useful in pandemic periods where social distancing is recommended., (© 2021 The Mediterranean Journal of Rheumatology (MJR).)

Sepsis remains to be a major contributor to mortality in ICUs, and immune suppression caused by immune cell apoptosis determines the overall patient survival. However, diagnosis of sepsis-induced lymphopenia remains problematic with no accurate prognostic techniques or biomarkers for cell death available. Developing reliable prognostic tools for sepsis-mediated cell death is not only important for identifying patients at increased risk of immune suppression but also to monitor treatment progress of currently trialed immunotherapy strategies. We have previously shown an important role for endoplasmic reticulum stress (ER stress) in inducing sepsis-mediated cell death and here report on the identification of a secreted form of the ER chaperone BiP (immunoglobulin binding protein) as a novel circulating prognostic biomarker for immune cell death and ER stress during sepsis. Using biochemical purification and mass spectrometry coupled with an established in vitro sepsis cell death assay, we identified BiP/Grp78 as a factor secreted by lipopolysaccharide-activated macrophages that is capable of inducing cell death in target cells. Quantitative ELISA analysis showed significantly elevated levels of circulating BiP in mice undergoing polymicrobial sepsis, which was absent in Bim -/- mice that are protected from sepsis-induced lymphopenia. Using blood serum from human sepsis patients, we could detect a significant difference in levels of secreted BiP in sepsis patients compared to nonseptic controls, suggesting that secreted circulating BiP could indeed be used as a prognostic marker that is directly correlative to immune cell death during sepsis., (© 2020 Federation of European Biochemical Societies.)

Sepsis is a biphasic disease characterized by an acute inflammatory response, followed by a prolonged immunosuppressive phase. Therapies aimed at controlling inflammation help to reduce the time patients with sepsis spend in intensive care units, but they do not lead to a reduction in overall mortality. Recently, the focus has been on addressing the immunosuppressive phase, often caused by apoptosis of immune cells. However, molecular triggers of these events are not yet known. Using whole-genome CRISPR screening in mice, we identified a triggering receptor expressed on myeloid cells (TREM) family receptor, TREML4, as a key regulator of inflammation and immune cell death in sepsis. Genetic ablation of Treml4 in mice demonstrated that TREML4 regulates calcium homeostasis, the inflammatory cytokine response, myeloperoxidase activation, the endoplasmic reticulum stress response and apoptotic cell death in innate immune cells, leading to an overall increase in survival rate, both during the acute and chronic phases of polymicrobial sepsis.

Sepsis and its impact on human health can be traced back to 1000 BC and continues to be a major health burden today. It causes about 11 million deaths world-wide of which, more than a third are due to neonatal sepsis. There is no effective treatment other than fluid resuscitation therapy and antibiotic treatment that leave patients immunosuppressed and vulnerable to nosocomial infections. Added to that, ageing population and the emergence of antibiotic resistant bacteria pose new challenges. Most of the deleterious effects of sepsis are due to the host response to the systemic infection. In the initial phase of infection, hyper activation of the immune system leads to cytokine storm, which could lead to organ failure and this accounts for about 15% of overall deaths. However, the subsequent immune paralysis phase (mostly attributed to apoptotic death of immune cells) accounts for about 85% of all deaths. Past clinical trials (more than 100 in the last 30 years) all targeted the inflammatory phase with little success, predictably, for inflammation is a necessary process to fight infection. In order to identify the regulators of immune cell death during sepsis, we carried out an unbiased, whole genome CRISPR screening in mice and identified Trigger Receptor Expressed in Myeloid-like 4 (Treml4) as the receptor that controls both the inflammatory phase and the immune suppression phase in sepsis (Nedeva et al. (2020) Nature Immunol, doi: 10.1038/s41590-020-0789-z). Characterising the Treml4 gene knockout mice revealed new insights into the relative roles of TLR4 and TREML4 in inducing the inflammatory cytokine storm during sepsis., Competing Interests: Conflict of interest: The authors declare no conflict of interests., (Copyright: © 2020 Menassa et al.)

BCL-2 family proteins regulate the mitochondrial apoptotic pathway. BOK, a multidomain BCL-2 family protein, is generally believed to be an adaptor protein similar to BAK and BAX, regulating the mitochondrial permeability transition during apoptosis. Here we report that BOK is a positive regulator of a key enzyme involved in uridine biosynthesis; namely, uridine monophosphate synthetase (UMPS). Our data suggest that BOK expression enhances UMPS activity, cell proliferation, and chemosensitivity. Genetic deletion of Bok results in chemoresistance to 5-fluorouracil (5-FU) in different cell lines and in mice. Conversely, cancer cells and primary tissues that acquire resistance to 5-FU down-regulate BOK expression. Furthermore, we also provide evidence for a role for BOK in nucleotide metabolism and cell cycle regulation. Our results have implications in developing BOK as a biomarker for 5-FU resistance and have the potential for the development of BOK-mimetics for sensitizing 5-FU-resistant cancers., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Sepsis is one of the leading causes of deaths world-wide and yet there are no therapies available other than ICU treatment. The patient outcome is determined by a complex interplay between the pro and anti-inflammatory responses of the body i.e., a homeostatic balance between these two competing events to be achieved for the patient's recovery. The initial attempts on drug development mainly focused on controlling inflammation, however, without any tangible outcome. This was despite most deaths occurring during the immune paralysis stage of this biphasic disease. Recently, the focus has been shifting to understand immune paralysis (caused by apoptosis and by anti-inflammatory cytokines) to develop therapeutic drugs. In this review we put forth an argument for a proper understanding of the molecular basis of inflammation as well as apoptosis for developing an effective therapy.

Aim: To calculate the prevalence of human leukocyte antigen (HLA)-B27 in axial spondyloarthritis patients (axSpA) compared to blood donors (BD) in Lebanon, to identify the clinical and radiological findings associated with HLA-B27 and to estimate the proportion of patients fulfilling the clinical arm of the Assessment of the Spondyloarthritis International Association (ASAS) criteria., Method: Consecutive Lebanese adult axSpA patients fulfilling the ASAS classification criteria were included from 12 rheumatology clinics across Lebanon. BD served as controls. A binary logistic regression was used to study the association between HLA-B27 and the disease features., Results: A total of 247 individuals were included (141 axSpA patients and 106 BD). The prevalence of HLA-B27 was 3.8% in BD and 41.1% in axSpA. Overall, 39.7% of the axSpA patients fulfilled the clinical arm of the ASAS classification criteria. Sensitivity of HLA-B27 for axSpA was 41.1%, specificity was 96.2%, positive predictive value was 93.6%, and negative predictive value was 55.13%. Positive likelihood ratio (LR) was 10.9 and negative LR was 1.63. We found a positive association of HLA-B27 with family history of SpA and psoriasis., Conclusion: Our study confirmed a low prevalence of HLA-B27 in axSpA patients and BD in this Lebanese population, However, we found a high specificity and positive LR, as well as the same number of axSpA patients fulfilling the clinical arm of the ASAS criteria as in European studies. HLA-B27 is therefore valuable for identification of axSpA in Lebanese patients despite the overall low prevalence in this population. Our results may guide future evaluations the role of HLA-B27 in planning local referral strategies., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Early diagnosis and early initiation of disease-modifying antirheumatic drug (DMARD) therapy slow the progression of joint damage and decrease the morbidity and mortality associated with rheumatoid arthritis (RA). According to the European League Against Rheumatism (EULAR) guidelines, treatment should be initiated with methotrexate and addition of biological DMARDs such as tumour necrosis factor (TNF) inhibitors should be considered for RA patients who respond insufficiently to methotrexate and/or other synthetic DMARDs and have poor prognostic factors. Africa and the Middle East is a large geographical region with varying treatment practices and standards of care in RA. Existing data show that patients with RA in the region are often diagnosed late, present with active disease and often do not receive DMARDs early in the course of the disease. In this review, we discuss the value of early diagnosis and remission-targeted treatment for limiting joint damage and improving disease outcomes in RA, and the challenges in adopting these strategies in Africa and the Middle East. In addition, we propose an action plan to improve the overall long-term outlook for RA patients in the region., (© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Purpose: To assess the effectiveness, safety, and comfort of transepithelial photorefractive keratectomy (PRK) using the Amaris laser platform., Setting: Ophthalmic Consultants of Beirut, Jal-El-Dib, Metn, Lebanon., Design: Comparative case series., Methods: Myopic eyes with or without astigmatism were treated by transepithelial PRK (study group) and compared with variable-adjusted eyes treated by conventional PRK (control group) during which the epithelium was removed with alcohol. Postoperative pain, epithelial healing time, uncorrected distance visual acuity (UDVA), manifest refraction, and haze were analyzed., Results: The mean subjective postoperative pain score (out of 10, indicating worst pain) at 48 hours was 2.0 in the study group (50 eyes) and 4.5 in the control group (50 eyes) (P=.02). The mean time to complete epithelial healing was 2.5 days ± 0.6 (SD) and 3.7 ± 0.8 days, respectively (P=.01). At 1 week, the UDVA was statistically significantly better in the control group; however, at 3 months, there was no statistically significant difference in UDVA, corrected distance visual acuity, or manifest refraction between the groups. Haze was significantly less in the study group (P<.01)., Conclusions: Transepithelial PRK for mild to moderate myopia with or without astigmatism was safe and easier to perform than conventional PRK, and patients had less pain, less postoperative haze, and a faster healing time. The visual outcomes with the 2 techniques were comparable., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Background: Currently, there is one Behçet's disease (BD) specific self reporting questionnaire developed and published in the literature, The Leeds BD-quality of life (QoL). We conducted a cross-cultural adaptation and validation of the Arabic version of the Leeds BD-QoL METHODS: A cross-sectional study was conducted among 41 consecutive patients attending rheumatology clinics at the American University of Beirut Medical Center between June and December 2007. The BD-QoL questionnaire, the Katz Index of Activities of Daily Living (ADL) and the Lawton Instrumental Activities of Daily Living (IADL) questionnaires were co-administered during the same visit, and severity scores were calculated. Cross-cultural adaptation of BD-QoL was performed using forward and backward translations of the original questionnaire. Internal consistency and test-retest reliability of the final version were determined. Exploratory Factor Analysis (EFA) was used to assess the dimensionality of the scale items. External construct validity was examined by correlating Arabic BD-QoL with the severity score, ADL and IADL., Results: The 30 items of the adapted Arabic BD-QoL showed a high internal consistency (KR-20 coefficient 0.89) and test-retest reliability (Spearman's test 0.91). The convergence of all 30 items suggests that the 30-item adapted Arabic BD-QoL scale is unidimensional. BD-QoL did not correlate with any of the patients' demographics. Still, it was positively correlated with patient severity score (r 0.4, p 0.02), and IADL (but not ADL)., Conclusions: This cross-cultural adaptation has produced an Arabic BD-QoL questionnaire that is now available for use in clinical settings and in research studies, among Arabic speaking patients.

Purpose: To review and report our experience in attempting to surgically eliminate the vertical deviations and the anomalous head posture in patients with inferior oblique palsy (IOP) and to add to the literature another etiology for IOP: denervation/myectomy of that muscle., Subjects and Methods: Seven patients demonstrating findings characteristic of an isolated IOP are reported. Six were unilateral and one was bilateral. All met the Bielschowsky/Parks' Three Step Test criteria to identify an isolated IOP. Six patients had surgery that consisted of weakening the superior oblique (SO) muscle of the affected eye alone or in combination with superior rectus recession of the fellow eye., Results: All patients were ultimately successfully alleviated of their vertical deviations and anomalous head postures. (Two patients developed an iatrogenic superior oblique palsy (SOP) which responded well to additional surgery.), Conclusions: The treatment of choice for IOP is tenotomy or tenectomy of the ipsilateral superior oblique muscle alone or in combination with recession of the contralateral superior rectus muscle.